C-11 cyanide production system

ABSTRACT

A method for providing  11 C-labeled cyanides from  11 C labeled oxides in a target gas stream retrieved from an irradiated high pressure gaseous target containing O 2 , wherein  11 C labeled oxides are reduced with H 2  in the presence of a nickel catalyst under a pressure and a temperature sufficient to form a product stream comprising at least about 95%  11 CH 4 , the  11 CH 4  is then combined with an excess of NH 3  in a carrier/reaction stream flowing at an accelerated velocity and the combined  11 CH4 carrier/reaction stream is then contacted with a platinum (Pt) catalyst particulate supported on a substantially-chemically-nonreactive heat-stable support at a temperature of at least about 900° C., whereby a product stream comprising at least about 60% H 11 CN is provided in less than 10 minutes from retrieval of the  11 C labeled oxide.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a divisional of U.S. patent application Ser. No.13/584,033, filed Aug. 13, 2012, which claims benefit of U.S.Provisional Application Ser. No. 61/524,121, filed on Aug. 16, 2011, theentire contents of both of which are incorporated herein by reference.

STATEMENT OF GOVERNMENT LICENSE RIGHTS

This invention was made with Government support under contract numberDE-AC02-98CH10886, awarded by the U.S. Department of Energy and undergrant number R21A1084189, awarded by the U.S. National Institutes ofHealth. The Government has certain rights in the invention.

FIELD OF THE INVENTION

The present invention relates generally to chemical processes forsynthesizing radioactive compounds for imaging, such as by positronemission tomography (PET). More particularly, the present inventionrelates to a compact, stand-alone instrument and method for producingC-11 cyanide (H¹¹CN) in a fast and efficient manner.

BACKGROUND

Positron emission tomography (PET) is a molecular imaging technologythat is increasingly used for detection of disease. PET imaging systemscreate images based on the distribution of positron-emitting isotopes inthe tissue of a patient. The isotopes are typically administered to apatient by injection of PET radiotracer probe molecules that comprise apositron-emitting isotope, (e.g. carbon-11, nitrogen-13, oxygen-15, orfluorine 18), covalently attached to a molecule that is readilymetabolized or localized in the body or that chemically binds toreceptor sites within the body. For PET radiotracer probes the shorthalf-lives of the positron emitting isotopes require that synthesis,analysis and purification of the probes are completed rapidly.

Carbon-11 (C-11) cyanide is a highly valuable precursor molecule for PETradiotracer synthesis by chemical transformations such as displacementand cross-coupling reactions. The resulting C-11 cyano-compounds canalso be converted to various functional groups such as amines, amides,carboxylic acids, which are abundant in various biological substrates,drugs and radiotracers. Various methods for synthesizing C-11 cyanideare known in the art. However, conventional C-11 cyanide productionsystems that are currently commercially available are large in size, notstand-alone or not cost-effective.

Moreover, due to the short half-life (20 min) of C-11, a shortproduction time is required. However, the production time involved intypical C-11 cyanide production systems of the prior art leave littleremaining time for useful analytic purposes.

Accordingly, there is a need to develop smaller or miniaturized systemsand devices that are capable of processing small quantities of molecularprobes. In addition, there is a need for such systems that are capableof expediting chemical processing to reduce the overall processing orcycle times, simplifying the chemical processing procedures, and at thesame time, provide the flexibility to produce a wide range of probes,biomarkers and labeled drugs, or drug analogs, inexpensively.

SUMMARY

The present method relates to providing ¹¹C labeled cyanides from ¹¹Clabeled oxides in a target gas stream retrieved from an irradiated highpressure gaseous target containing O₂. The method generally includes:

-   -   (i) reducing ¹¹C labeled oxides with H₂ in the presence of a        nickel catalyst under a pressure and a temperature sufficient to        form a product stream comprising at least about 95% ¹¹CH₄;    -   (ii) combining the ¹¹CH₄ with an excess of NH₃ in a        carrier/reaction stream flowing at an accelerated velocity; and    -   (iii) contacting the combined ¹¹CH₄ carrier/reaction stream with        a platinum (Pt) catalyst particulate supported on a        substantially-chemically-nonreactive heat-stable support at a        temperature of at least about 900° C., and more preferably is at        least about 940° C., whereby a product stream comprising at        least about 60% H¹¹CN is provided in less than 10 minutes from        retrieval of the ¹¹C labeled oxides.

In a preferred embodiment, the method further includes mixing the ¹¹CH₄and NH₃ carrier/reactant stream prior to contacting the stream with thePt catalyst at elevated temperature. The method further preferablyincludes removing unreacted ¹¹CO₂ from the product stream resulting fromstep (i) to provide a cleansed ¹¹CH₄ product stream of increased ¹¹CH₄content. The act of removing preferably includes passing the productstream resulting from step (i) through a soda lime trap whereby ¹¹CO₂ isscrubbed from the stream.

The act of reducing preferably includes passing a pressurized stream of¹¹CO₂, NH₂, and N₂ through a heated zone packed with a mixture of nickel(Ni) catalyst powder and a molecular sieve, such heated zone having anentrance and an exit. The heated zone is preferably arranged withsubzones of substantially all nickel catalyst powder at the entrance ofthe zone and at the exit of the zone so that the nickel-only subzonessandwich a third subzone which houses the mixture of the nickel powderand the molecular sieve. The molecular sieve is provided in an amountsufficient to trap substantially all of the nonreacted ¹¹CO₂ present inthe pressurized stream for subsequent desorption in the presence of heatfor reduction to ¹¹CH₄.

The act of flowing at accelerated velocity includes passing NH₃ gas tothe combining of (ii) at a rate of at least about 550 ml/min up to aspeed which permits substantially complete reaction of the ¹¹CH₄ in thecombined stream to form H¹¹CN. The accelerated velocity for passing theNH₃ gas is preferably a rate from about 600 ml/min to about 700 ml/min,and more preferably, a rate from about 640 ml/min to about 660 ml/min.

In a preferred embodiment, the platinum catalyst particulate of (iii) isplatinum black and the substantially-chemically-nonreactive heat-stablesupport is a molecular sieve, which is heat stable up to at least 1500°C.

The present method includes miniaturizing a reaction furnace having areaction chamber for reacting ¹¹CH₄ with NH₃ to form H¹¹CN in thepresence of a platinum catalyst. The method generally includes:

-   -   (i) supporting platinum particulate with a        substantially-chemically-nonreactive heat-stable support; and    -   (ii) minimizing the size of said reaction chamber for housing        said supported platinum particulate to obtain high efficiency        H¹¹CN conversion from a reaction stream passed therethrough,        said reaction stream comprising substantially ¹¹CH₄ and NH₃,        whereby the size of said furnace can be miniaturized.

In a preferred embodiment, the platinum particulate is platinum blackand the substantially-chemically-nonreactive heat-stable support is amolecular sieve. The step of minimizing preferably means providing achamber having a volume not greater than about 30 cubic centimeters.

The present method further involves optimizing the conversion of ¹¹CO₂to form ¹¹CH₄ by reducing ¹¹CO₂ with H₂ using nickel catalyst. Themethod generally includes:

-   -   (i) passing a ¹¹CO₂ stream with a stream of N₂ and H₂ under        pressure through a chemical reduction zone having an entry and        an exit, such zone subdivided into three subzones, an entry        subzone, a middle subzone, and an exit subzone, the entry and        exit subzones are provided with a substantially only        nickel-catalyst powder and the middle subzone is provided with a        mixture of nickel catalyst powder and molecular sieve; and    -   (ii) heating the chemical reduction zone to promote such        reduction, whereby ¹¹CO₂ is at least partially reduced in the        entry and exit subzone while the substantial balance of ¹¹CO₂ is        absorbed by the molecular sieve and is subsequently desorbed        therefrom in the presence of heat and substantially completely        reduced in the presence of the nickel powder.

A present system is also provided and relates to producing H¹¹CN gasfrom ¹¹C-labeled oxides in less than ten (10) minutes. The presentsystem generally includes a ¹¹CO₂ inlet conduit for receiving andconveying ¹¹CO₂ gas from a target, a H₂ inlet conduit for receiving andconveying H₂ gas from a source, a N₂ inlet conduit for receiving andconveying N₂ gas from a source, a nickel furnace fluidly connected withthe ¹¹CO₂ inlet, the H₂ inlet and the N₂ inlet for receiving the ¹¹CO₂gas, the H₂ gas and the N₂ gas respectively therefrom. The furnace heatsthe ¹¹CO₂ gas, the H₂ gas and the N₂ gas in the presence of a nickelcatalyst contained therein to produce ¹¹CH₄ gas. A ¹¹CH₄ conduit isconnected to an outlet of the nickel furnace for receiving and conveyingthe ¹¹CH₄ gas from the nickel furnace, a NH₃ inlet conduit for receivingand conveying NH₃ gas from a source, a platinum furnace fluidlyconnected with the ¹¹CH₄ conduit and the NH₃ inlet conduit for receivingthe ¹¹CH₄ gas and the NH₃ gas respectively therefrom and for heating the¹¹CH₄ gas and the NH₃ gas in the presence of a platinum catalyst. Theplatinum furnace produces H¹¹CN gas and a H¹¹CN outlet conduit isfluidly connected to an outlet of the platinum furnace for receiving andconveying the H¹¹CN gas from the platinum furnace. The ¹¹CO₂ inletconduit, the H₂ inlet conduit, the N₂ inlet conduit, the nickel furnace,the ¹¹CH₄ conduit, the NH₃ inlet conduit, the platinum furnace and theH¹¹CN outlet conduit collectively define a total system gaseous volumeof about less than 18 mL whereby the system provides a total systemcycle time for producing H¹¹CN gas of less than ten (10) minutes. In apreferred embodiment, the system occupies a space less than or equal toabout 20 cm×28 cm×27 cm.

Also, the system preferably includes a soda lime trap disposed in the¹¹CH₄ conduit for removing unreacted ¹¹CO₂ gas from the ¹¹CH₄ conduit.The system preferably further includes a mixer fluidly connected withthe ¹¹CH₄ conduit and the NH₄ inlet conduit for respectively receivingand mixing the ¹¹CH₄ gas and the NH₃ gas from the ¹¹CH₄ conduit and theNH₃ inlet conduit.

The nickel furnace preferably includes an alumina tube and an electricalresistance heating wire wrapped around the alumina tube. The aluminatube preferably has a length of about 4.5 cm, an outer diameter of about1.3 cm and an inner diameter of about 0.95 cm.

The platinum furnace preferably includes an alumina tube and anelectrical resistance heating wire wrapped around the alumina tube. Thealumina tube preferably has a length of about 15 cm, an outer diameterof about 2 cm and an inner diameter of about 1.6 cm.

The preferred embodiments of the present C-11 cyanide production systemand the method for producing C-11 cyanide, as well as other objects,features and advantages of this invention, will be apparent from thefollowing detailed description, which is to be read in conjunction withthe accompanying drawings. The scope of the invention will be pointedout in the claims.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a schematic drawing of the present C-11 cyanide productionsystem.

FIG. 2 is a side view of the nickel furnace of the system shown in FIG.1.

FIG. 3 is a cross-sectional view of the soda lime trap of the systemshown in FIG. 1.

FIG. 4 is a cross-sectional view of the mixer of the system shown inFIG. 1.

FIG. 5 is a side view of the platinum furnace of the system shown inFIG. 1.

FIG. 6 is a diagrammatic side view of an embodiment for rapidly coolingthe nickel furnace of the present invention.

FIG. 7 is a schematic diagram of an alternative embodiment of thepresent invention, wherein two nickel furnaces are provided in parallel.

FIG. 8 is a diagrammatic cross-sectional view of a preferred embodimentof a nickel catalyst package used in the nickel furnace of the presentinvention.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

Referring first to FIG. 1, the present system 10 is generally acombination of commercially available and custom design componentsprovided in a miniaturized form in order to provide a compact andefficient system for producing C-11 cyanide (H¹¹CN) gas. This system 10is preferably supported on a compact “mother board” frame or plate (notshown) having overall dimensions of approximately 20 cm (D)×28 cm (W)×27cm (H). Hardware for attaching the components to the frame or platepreferably take the form of clips or other such brackets fixed to theplate or frame, which allow for quick and releasable plug-in connectionof the various components. As a result, easy access and quickreplacement of the components is provided with the system 10 of thepresent invention.

The present system 10 includes four inlet ports 12, 14, 16, 18 forintroducing the necessary process gases to the system. The inlet ports12, 14, 16, 18 are preferably in the form of needle valves, or othertype of quick-connect devices for connecting flexible hoses or otherconduits from their respective gas sources. Inlet port 12 receivesradioactive C-11 carbon-dioxide (¹¹CO₂) gas from a target source. Inletport 14 receives nitrogen (N₂) gas from a source. Inlet port 16 receiveshydrogen (H₂) gas from a source and inlet port 18 receives ammonia (NH₃)gas from a source.

Immediately down-stream of each inlet port 12, 14, 16, 18 is a 2-waysolenoid valve 20, 22, 24, 26 and a flow control valve 28, 30, 32 and 34for controlling and regulating the flow of the respective process gasinto the system. Also, preferably provided on at least the nitrogen (N₂)inlet port 14 and the ammonia (NH₃) inlet port 18 are pressureregulators 36, 38 to control the respective pressure of the nitrogen andammonia gases entering the system.

The solenoid valves, control valves, pressure regulators and needlevalves are generally commercially available parts but are selected toprovide a small cross-sectional flow. Similarly, the tubing or conduitsfor conveying the process gases between the various components of thesystem have a relatively small cross-section of equal to or less thanabout 0.2 cm to minimize the overall volume of the gas in the system. Asa result, the overall flow cycle time is reduced and, as will bediscussed in further detail below, the conditioning time (i.e., the timerequired to initially bring the system to operational condition) canalso be reduced.

The C-11 carbon dioxide (¹¹CO₂) inlet 12, the nitrogen (N₂) inlet 14 andthe hydrogen (H₂) inlet 16 are all disposed upstream and are fluidlyconnected to a nickel furnace 40. A pressure gauge 42 is also preferablyprovided upstream of the nickel furnace for monitoring the pressure ofthe process gases entering the nickel furnace. The pressure gauge 42 isconnected to a vent 46 via a 3-way solenoid valve 48 for venting processgasses should the pressure get too high.

The C-11 carbon dioxide (¹¹CO₂) line 12A, the nitrogen (N₂) line 14A andthe hydrogen (H₂) line 16A all preferably meet and feed into a singletwo way solenoid valve 44 located immediately upstream of the nickelfurnace 40. The two way nickel furnace inlet solenoid valve 44 providesfor a single shut-off of all gases entering the nickel furnace ifrequired.

As shown additionally in FIG. 2, the nickel furnace 40 is a customdesigned, miniaturized furnace, which permits extremely rapid heat-upand cool-down time, as compared to nickel furnaces used in conventionalC-11 cyanide production systems. The nickel furnace 40 includes acommercially available alumina tube 50 having a length of about 4.5 cm,an outer diameter of about 13 mm and an inner diameter of about 9.5 mm.A length of Kanthal A-1® electrical heating wire 52 is tightly wrappedaround the outer surface of the alumina tube 50. The wire 52 preferablyextends along the central axial length of the tube 50 to create aheating zone 54 having a length of about 3.8 cm. Opposite ends of thewire 52 are preferably provided with electrical terminals or areotherwise exposed to allow for connection to an electric source.

The wire 52 preferably has a resistance of 4.147 ohms/foot to provide atotal resistance of 32 ohms. Therefore, providing a current of 3.75 Awould produce a heater producing 450 W. With this design, the nickelheater 40 can be heated from room temperature to 400-450° C. inapproximately 10-15 seconds.

The electrical heating wire 52 can be fixed to the tube 50 using acommercially available ceramic paste. Alternatively, the wire 52 can bereleasable from the tube 50 to enable a rapid cool-down of the tube. Inparticular, the wire 52 and the tube 50 can be assembled to allow thepre-formed coiled wire to be axially translated away from the tube inorder to separate the tube from the still hot wire after the heatingprocess is complete, as shown in FIG. 6. In this manner, the tube 50will cool down faster than the heating wire, which will provide aquicker cycle time to repeat the process.

Another way to improve cycle time of the system, with respect to theheating and cooling time required for the nickel furnace 40, is toprovide the system with two nickel furnaces 40 a and 40 b in parallel,as shown in FIG. 7. Thus, while one of the furnaces 40 a, for example,is in use and being heated, the other furnace 40 b is not in use and isbeing cooled. In this case, a three-way valve 55 is provided to divertthe incoming gas to the furnace 40 a in use, while the other furnace 40b cools. Once the reaction is complete in the furnace 40 a in use, thereacted gas is evacuated and this furnace 40 a is allowed to cool down.In the meantime, once the idle furnace 40 b is sufficiently cool, thethree-way valve 55 switches over to divert gas to this furnace 40 b,while the other furnace 40 a cools. The result is a dramatic reductionin system down-time, which would otherwise be required to allow a singlenickel furnace to cool after each cycle.

In any case, the nickel furnace 40 contains a nickel catalyst, which isused to react the C-11 carbon dioxide (¹¹CO₂) gas fed to the furnace.The nickel catalyst is preferably provided in a nickel catalyst package57, as shown in FIG. 8, which can be inserted into the tube 50 of thenickel furnace 40. The nickel catalyst package 57 is preferably about2.5-3.0 cm long and is divided into subzones. A central subzone isdefined by a molecular sieve 59 and an entrance subzone 61 a and an exitsubzone 61 b are respectively defined by two nickel plugs 62 boundingopposite ends of the sieve 59.

The sieve 59 is preferably a 4 A 80/100 mesh sieve. A suitable molecularsieve for use in the present system is available at Grace DavisonDiscovery Science—Catalog: 5624 (www.discoverysciences.com). The sieve59 captures an amount of nickel catalyst powder for trapping un-reactedC-11 carbon dioxide (¹¹CO₂) gas. A suitable nickel catalyst powder canbe obtained from Shimadzu Corp. under the trade name of Shimalite-Ni(reduced), P/N 221-27719, Lot No. S91461. In a preferred embodiment,about 130 mg nickel powder is captured in 260 mg of nickel sieve.

The nickel plugs 62 are essentially high concentration nickel catalystpowder packed together to form a relatively dense disc-shaped element,as compared to the sieve 59. In a preferred embodiment, each nickel plug62 contains about 20 mg of nickel powder. This results in a nickelpackage 57 having a nickel/molecular sieve ratio of about 170 mg/260 mg.

It has been found with conventional nickel catalyst packages, whichtypically consist of only a molecular sieve containing the nickelcatalyst without nickel end plugs, most of the chemical reaction occursat the gas entrance and exit portions of the sieve. As a result, theends of conventional nickel catalyst packages are typically depleted ofnickel catalyst well before the center portion of the package.

By providing a higher concentration of nickel, in the form of nickelplugs 62, at the entrance and exit regions of the package 57 with thepresent system on, more efficient use of the nickel catalyst can beachieved. Specifically, the nickel package 57 of the present systemoptimizes the process of conversion of ¹¹CO₂ to form ¹¹CH₄ by reducing¹¹CO₂ with H₂ using nickel catalyst.

Thus, a ¹¹CO₂ stream with a stream of N₂ and H₂ is passed under pressurethrough the nickel package 57 in the nickel furnace 40, wherein thenickel package forms a chemical reaction zone having an entry and anexit. The chemical reaction zone is subdivided into an entry subzone 61a, a middle subzone 61 c, and an exit subzone 61 b, wherein the entryand exit subzones are provided with a nickel catalyst powder in aconcentrated form (i.e., the nickel plugs 62) and the middle subzone isprovided with a mixture of nickel catalyst powder and molecular sieve59. The chemical reduction zone is then heated to promote the reduction,whereby ¹¹CO₂ is at least partially reduced in the entry and exitsubzone while the substantial balance of ¹¹CO₂ is absorbed by themolecular sieve and is subsequently desorbed therefrom in the presenceof heat and substantially completely reduced in the presence of thenickel powder.

As a result, the package 57 can be made smaller, while providing thesame amount of nickel catalyst as compared with conventional nickelcatalyst packages. In turn, by making the nickel catalyst package 57smaller, the nickel furnace 40, and thus the entire system can be madesmaller.

Returning to FIG. 1, a first radiation detector 56 and a cooling fan 58are preferably provided immediately adjacent to the nickel furnace 40.The first radiation detector 56 is provided to monitor un-reacted C-11carbon dioxide (¹¹CO₂) gas in the nickel furnace 40, while the coolingfan 58 is provided to provide for rapid cooling the nickel furnace oncethe reaction time is complete. With the cooling fan 58 provided, theheat nickel furnace 40 can cool from 450° C. to room temperature inapproximately 15 minutes.

Connected to the outlet of the nickel furnace 40 is a nickel furnaceoutlet line 60 for delivering reacted gas from the nickel furnacefurther along the system. Preferably provided in the nickel outlet line60 is a two-way solenoid valve 63 which allows for the control ofreacted gas entering the outlet line 60 from the nickel furnace 40. Theoutlet line 60 further preferably includes a three-way solenoid valve 64for diverting converted C-11 methane (¹¹CH₄) gas and un-reacted C-11carbon dioxide (¹¹CO₂) gas from the system. A second three-way solenoidvalve 66 can be provided to further divert the converted C-11 methane(¹¹CH₄) gas and/or the un-reacted C-11 carbon dioxide (¹¹CO₂) gas to avent 68 or an access outlet 70.

The converted C-11 methane (¹¹CH₄) gas not diverted from the system 10is then fed into a sodalime trap inlet line 72, which feeds the C-11methane (¹¹CH₄) gas to a sodalime trap 74. As shown additionally in FIG.3, the sodalime trap 74 is customized and designed on a miniaturizedscale, to remove unwanted C-11 carbon dioxide (¹¹CO₂) from the system.The sodalime trap 74 is essentially a narrow tube 76 having an amount ofsodalime 78 contained therein. The tube 76 includes a removeable cap 80threaded at one end of the tube to permit replenishment of the sodalime78 in the trap 74 as needed. The cap preferably includes an inlet 82 forconnection to the sodalime inlet line 72. Provided at the opposite endof the tube 76 is an outlet 84 for connection to a sodalime outlet line86.

The sodalime trap 74 removes essentially all of the un-reacted C-11carbon dioxide (¹¹CO₂) from the system. In this regard, a secondradiation detector 88 is preferably provided adjacent the sodalime trap74 to monitor any un-reacted C-11 carbon dioxide (¹¹CO₂).

The sodalime outlet line 86 meets with an ammonia (NH₃) line 90, whichfeeds ammonia gas from the ammonia inlet 18 to the system. The ammonia(NH₃) line 90 and the sodalime trap outlet line 86 feed a mixer 92,which mixes the ammonia (NH₃) gas and the C-11 methane (¹¹CH₄) gas.

As additionally shown in FIG. 4, the mixer 90 is also a custom made partthat provides efficient mixing on a small scale. The mixer 90 includes atube 90 having a cap 94 connected at an inlet end of the tube and anoutlet 96 connected at the opposite end of the tube. The cap 94 ispreferably connected to the inlet end of the tube 92 via a threadedconnection to allow for removal of the cap as needed.

The cap is formed with a needle nozzle 98 which extends into theinterior of the tube 92. The needle nozzle 98 is closed at its distalend and is provided with a plurality of apertures 100 through which gasfed into the interior of the nozzle may exit. Extending outwardly fromthe cap in a direction opposite to the inward direction of the needlenozzle 98 is an inlet port 102 for connection with a mixer inlet line104, which in turn is connected with the sodalime outlet trap 86 and theammonia (NH₃) inlet line 90. An internal conduit 106 extends from thecap inlet 102 to the needle nozzle 98 and is in fluid communication withthe plurality of apertures 100 formed in the needle nozzle. Thus, gasflowing from the mixer inlet line 104 into the mixer 90 exits throughthe apertures 100 of the needle nozzle 98 into the interior of the tube92 in a manner which will provide efficient mixing of the ammonia (NH₃)and the C-11 methane (¹¹CH₄) gases.

A platinum furnace inlet line 108 is connected to the outlet 96 of themixer 90 for delivering the mixed ammonia (NH₃) and C-11 methane (¹¹CH₄)gases to a platinum furnace 110. As shown additionally in FIG. 5, theplatinum furnace 110 is also a custom made part designed with the goalsof miniaturization and rapid heating in mind. In this regard, theplatinum furnace includes a quartz tube 112 wrapped with a Kanthal A-1®electrical heating wire 114. The quartz tube is preferably about 150 mmin length, having an outer diameter of 20 mm and an inner diameter of 16mm. The wire 114 is wrapped around the outer surface of the quartz tube112 along a central length of the tube to provide a heating zone 116 ofapproximately 100 mm in length. The Kanthal A-1® heating wire 114preferably has a 24 AWG, a length of about 6.8 meters and a diameter of1 mm. The wire has a maximum operating temperature of between 1350-2460°C. and is applied to the quartz tube 112 with a commercially availableceramic paste. Opposite ends of the wire are preferably provided withelectrical terminals or are otherwise exposed to allow for connection toan electric source.

The platinum furnace 110 further contains an amount of platinum catalystfor converting the mixed ammonia (NH₃) and C-11 methane (¹¹CH₄) gases toC-11 cyanide (H¹¹CN) gas. The platinum catalyst is provided as aparticulate supported on a substantially chemically non-reactive, heatstable support. The support can be provided in the form of a 3-5platinum gauze. For example, two platinum gauze pieces, (Product Number:298107-1.7G), having a 5 cm×5 cm size and totaling about 2-9 grams canbe packed in the quartz tube.

However, in a preferred embodiment, the platinum black powder iscaptured or otherwise supported in a molecular sieve. Thus, a molecularsieve is preferably utilized as the platinum black powder support. Anycommercially available 100% platinum black powder can be used. Asuitable platinum black catalyst powder is supplied by EngelhardIndustries, Inc., 113 Astor Street, Newark, N.J. under for example, Lot#10-077. The molecular sieve preferably has a size of about 4 Angstroms.

It has been surprisingly found that a molecular sieve supportingplatinum black provides an efficient means for providing platinum to thehigh-temperature reaction within the platinum furnace 110. Specifically,the surface area of available platinum is greatly increased bysupporting platinum black in the molecular sieve. The lower limit of theamount of platinum black provided in the sieve is determined by theamount sufficient to catalyze the mixed ammonia (NH₃) and C-11 methane(¹¹CH₄) gases to C-11 cyanide (H¹¹CN). The upper limit of the amount ofplatinum black provided in the sieve is determined by the amount atwhich platinum coagulation will occur within the platinum furnace tube.

A platinum furnace outlet line 118 is fluidly connected to the platinumfurnace outlet for removing reacted C-11 cyanide (H¹¹CN) gas from theplatinum furnace 110. A two-way solenoid valve 120 and a flow meter 122are provided in the platinum furnace outlet line 118 to regulate theflow of the C-11 cyanide (H¹¹CN) gas from the platinum furnace 110. Athree-way solenoid valve 124 is also preferably provided in the platinumfurnace outlet line 118 to selectively allow for extraction of the C-11cyanide (H¹¹CN) gas from the system or to divert the C-11 cyanide(H¹¹CN) gas back to the three-way solenoid valve 48 provided in thereacted gas lines 12A, 14A, 16A to divert the cyanide gas to the vent46.

Having described the components of the system 10, operation of thesystem will now be described in the following EXAMPLE of an actual useof the system, with reference to the drawings.

EXAMPLE

Radioactive C-11 carbon dioxide (¹¹CO₂) gas was taken from a target anddelivered to the nickel furnace 40 upon the opening of solenoid valves20, 44, 63 and 64. Once the first radiation detector 56 hit its plateauall valves were closed. Solenoid valves 44 and 24 were then opened tofeed hydrogen (H₂) gas to the nickel furnace. Once the pressure gage 42reached 10-15 psi, the solenoid valves 44 and 24 were closed. Nitrogengas was then introduced at a pressure of about 8.5 psi. This processingstep took about 2 minutes.

The nickel furnace 40 was then heated to 450° C. in less than oneminute. Once at operating temperature, the carbon dioxide was heated forabout 3 minutes to convert the C-11 carbon dioxide (¹¹CO₂) gas to C-11methane (¹¹CH₄) gas. During heating, the cooling fan 58 was turned off.Once heating was complete, the solenoid valves 26 and 120 were opened torelease the converted C-11 methane (¹¹CH₄) gas to the platinum furnace110, which had been preheated to 950° C. Preheating of the platinumfurnace took about 10 minutes.

Ammonia gas was then fed to the system at a pressure of about 6.5 psi.The ammonia gas was mixed with the methane gas in the mixer 90 and wasdelivered to the platinum furnace. The platinum furnace 110 convertedthe C-11 methane (¹¹CH₄) gas to a product stream containing about 80%C-11 cyanide (H¹¹CN) gas. This step took about 2 minutes.

To cool the nickel furnace 40, solenoid valves 24, 44, 63 and 64 wereopened to allow hydrogen (H₂) to flow. The cooling fan 58 was now turnedon until the nickel furnace 40 cooled to below 30° C.

C-11 cyanide (H¹¹CN) gas production results utilizing platinum blackcatalyst powder supported in a molecular sieve are as follows:

Run #1

1 min beam: 50-70 mCi

After 9 mins—End of Beam (BOB): 22.4 mCi

Run #2

After 7 mins—EOB: 24.1 mCi

Run #3

After 7 mins—EOB: 22.6 mCi

Thus, the present system utilizes custom designed furnaces, which arecapable of heating to adequate temperatures for both reduction of CO₂(preferably, 420° C.) and formation of C-11 CN (preferably 800-900° C.)within 20 min to be ready for the production from the start. The wholesynthesis time is 6 min, which is faster than commercially availablesystems (about 10 min). Also, the recycle time is 10 min (i.e., every 10min, another batch of C-11 CN can be produced).

It is also conceivable that the system of the present invention can beequipped with multiple ¹¹CO₂ (nickel)/¹¹CH₄ (platinum) furnaces, whichallows more than two productions consecutively without delaying toaccommodate a demanding production schedule.

The present system is stand-alone and small enough to be portable (20 cm(D)×28 cm (W)×27 cm (H)), as long as the sources of gases are connected.The product ion control for synthesis can be controlled by one-button(work-away mode) or step-by-step modes. If needed, each valve or furnacecan be controlled manually in case of emergency. The control box module(35.5 cm (L)×25.5 cm (W)×8 cm (H)) is connected to a conventionalcomputer. The function of each module is designed to work independentlyand at the same time, if combined, the whole system works as oneintegrated production system. The radiochemical yield in theprototypical system is high (60-80%) and production has been shown to bereproducible over 100 times.

As a result of the present system, a cost-effective, stand-alone, andhigh yielding C-11 cyanide system is provided, which is also verycompact and small enough to be workable in a conventional shielded hoodof a laboratory. Thus, the small size of the present system requiresless lead shielding.

The present system is also highly flexible to produce other C-11 labeledsmall molecules itself or integrated with the production of other smallmolecules such as ¹¹CO₂, C-11 methane, and C-11 carbon monoxide. Thesystem also affords a functional modular design with flexibility forfunctional combination to produce other C-11 molecules with a shortproduction time and recycling time for production schedule.

Although preferred embodiments of the present invention have beendescribed herein with reference to the accompanying drawings, it is tobe understood that the invention is not limited to those preciseembodiments and that various other changes and modifications may beaffected herein by one skilled in the art without departing from thescope or spirit of the invention, and that it is intended to claim allsuch changes and modifications that fall within the scope of theinvention.

The invention claimed is:
 1. A system for producing H¹¹CN gas from¹¹C-labeled oxides in less than nine (9) minutes, the system comprising:a ¹¹CO₂ inlet conduit for receiving and conveying ¹¹CO₂ gas from atarget; a H₂ inlet conduit for receiving and conveying H₂ gas from asource; a N₂ inlet conduit for receiving and conveying N₂ gas from asource; a heated nickel furnace, said furnace having an entrance and anexit and arranged with a first subzone and a second subzone ofsubstantially all nickel catalyst powder, wherein the first subzone isarranged at said entrance of said heated zone and the second suchsubzone is arranged at said exit of said heated zone, wherein said firstand second subzones sandwich a third subzone which houses a mixture ofnickel (Ni) catalyst powder and a molecular sieve, fluidly connectedwith said ¹¹CO₂ inlet, said H₂ inlet and said N₂ inlet for receiving the¹¹CO₂ gas, the H₂ gas and the N₂ gas respectively therefrom, and forheating the ¹¹CO₂ gas, the H₂ gas and the N₂ gas in the presence of anickel catalyst contained within said nickel furnace to produce ¹¹CH₄gas; a ¹¹CH₄ conduit connected to an outlet of said nickel furnace forreceiving and conveying the ¹¹CH₄ gas from said nickel furnace; a NH₃inlet conduit for receiving and conveying NH₃ gas from a source; aplatinum furnace fluidly connected with said ¹¹CH₄ conduit and said NH₃inlet conduit for receiving the ¹¹CH₄ gas and the NH₃ gas respectivelytherefrom and for heating the ¹¹CH₄ gas and the NH₃ gas in the presenceof a platinum catalyst contained within said platinum furnace to produceH¹¹CN gas; and a H¹¹CN outlet conduit fluidly connected to an outlet ofsaid platinum furnace for receiving and conveying the H¹¹CN gas fromsaid platinum furnace, wherein said ¹¹CO₂ inlet conduit, said H₂ inletconduit, said N₂ inlet conduit, said nickel furnace, said ¹¹CH₄ conduit,said NH₃ inlet conduit, said platinum furnace and said H¹¹CN outletconduit collectively define a total system gaseous volume of about lessthan 18 mL whereby the system provides a total system cycle time forproducing H¹¹CN gas of less than nine (9) minutes.
 2. A system accordingto claim 1, wherein the system occupies a space less than or equal toabout 20 cm×28 cm×27 cm.
 3. A system according to claim 1, furthercomprising a soda lime trap disposed in said ¹¹CH₄ conduit for removingunreacted ¹¹CO₂ gas from said ¹¹CH₄ conduit.
 4. A system according toclaim 1, further comprising a mixer fluidly connected with said ¹¹CH₄conduit and said NH₄ inlet conduit for respectively receiving and mixingthe ¹¹CH₄ gas and the NH₃ gas from said ¹¹CH₄ conduit and said NH₃ inletconduit.
 5. A system according to claim 1, wherein said nickel furnacefurther comprises an alumina tube and an electrical resistance heatingwire wrapped around said alumina tube, said alumina tube having a lengthof about 4.5 cm, an outer diameter of about 1.3 cm and an inner diameterof about 9.5 mm.
 6. A system according to claim 1, wherein said platinumfurnace comprises a quartz tube and an electrical resistance heatingwire wrapped around said quartz tube, said quartz tube having a lengthof about 15 cm, an outer diameter of about 2 cm and an inner diameter ofabout 1.6 cm.
 7. A system according to claim 2 further comprising asecond heated nickel furnace fluidly connected via a three-way valve tosaid heated nickel furnace and said ¹¹CO₂, H₂ and N₂ gas inlets.